The emergence of new animal models that mimic human disorders has enabled innovative, fundamental and therapeutic approaches to medical research. Mice, rats, and guinea pigs have become ubiquitous participants in most areas of molecular biology, toxicology, and drug discovery research. Well-characterized models have been developed to enable the study of a wide range of diseases and offer the possibility of studying the fundamental mechanisms of such diseases, as well as provide opportunities to test the effectiveness of potential drugs. As a result, there has been an increase in demand for effective imaging technologies, especially those directed to in vivo small animal imaging. Effective small animal imaging provides keen insights into human physiology and disease processes. For example, such information is particularly important in the area of gene therapy, where an imaging system can be used to assess the success of vector delivery and obtain accurate time curves of gene expression. Effective in vivo imaging technologies may also help researchers expedite pre-clinical drug development processes, potentially saving numerous years and thousands of dollars on drugs that may ultimately not prove to be efficacious and/or safe.
Single photon emission computed tomography (SPECT) and photon emission tomography (PET) are nuclear imaging procedures that can be used to perform in vivo small animal imaging. High-resolution SPECT systems are commonly used in tracer development and pre-clinical research where new radiopharmaceuticals have to be tested and evaluated in small-animal studies. The fundamental principle underlying nuclear imaging is the use of agents, which localize in specific organs or tissue on the basis of their biochemical or physiological properties. Typically one or more radiopharmaceuticals or radioisotopes are injected into the subject bloodstream. The injected radiopharmaceuticals are absorbed by and accumulate in the selectively targeted subject organ. The accumulated radiopharmaceuticals emit energy in the form of gamma rays or photons that illuminate the target organ. A nuclear imaging system, such as for example a SPECT imaging system, is used to create an image of the distribution of the accumulated radioactive pharmaceutical within the target organ within the subject.
Nuclear imaging is performed using a gamma ray imaging device that consists of a gamma ray detector and a collimator. One or more gamma ray imaging devices are typically placed adjacent to a surface of the subject to monitor and record the radiation emitted by the target organ. The gamma rays emitted by the target organ are collimated or sorted by the collimator and recorded by the gamma detector.
Each gamma ray detector typically includes a scintillation crystal which produces a flash or scintillation of light each time it is struck by radiation emanating from the radioactive dye in the subject. An array of photomultiplier tubes and associated circuitry produces an output signal which is indicative of the (x, y) position of each scintillation on the crystal. The one or more gamma ray imaging devices are typically are rotated or indexed around the subject to monitor the emitted radiation from a plurality of different angles to obtain multiple two dimensional images of the subject target organ. The collected two dimensional images are used to compute or reconstruct a three dimensional volumetric representation of the target organ.
The computed tomographic images reveal physiology and cellular metabolism. With the use of specific radiotracers, radio imaging techniques can provide various forms of metabolic information, such as for example, functional and oncological imaging, the evaluation of new radiopharmaceuticals for increased diagnostic efficacy, the evaluator or new receptor ligands, and reporter gene expression imaging.
When gamma ray imaging devices are used in small animal imaging, the detection sensitivity and the spatial resolution of a projected image of the subject target organ often depends upon the geometry of the collimation system. One prior art collimator, a parallel hole collimator, is routinely employed in small animal imaging, however the parallel hole collimation is typically not geometrically efficient for small animal imaging.
Another prior art collimator often used in small animal imaging is a single pinhole collimator. The single pinhole collimator provides generally high spatial resolution and reasonable sensitivity when the subject is placed in close proximity to the pinhole. A single pinhole collimator generates a cone beam imaging geometry. A large cone angle, as typically generated by a single pinhole collimator, generally provides relatively large image magnification, which in turn results in greater spatial resolution. However, a large cone-angle also causes a data insufficiency problem which translates into increased distortion and artifact severity in a reconstructed three dimensional image. The severity of artifact is generally proportional to the cone-angle of the single pinhole in the direction of the axis of rotation. Increasing the distance between the single pinhole collimator and the subject, thereby generating a smaller cone angle, may decrease the severity of artifacts. However, sensitivity is also decreased when the single pinhole collimator-to-subject distance is increased.
Another prior art collimator often employed when imaging small animals is a multiple pinhole collimator. The multiple pinhole collimator, having a plurality of pinholes, typically reduces cone-beam related artifact effects and increases detection sensitivity by tiling the detector with multiple cone-beam images. The multiple pinhole collimator is typically placed relatively farther away from the subject than a single pinhole collimator thereby generating smaller cone angles. The use of smaller cone angles typically mitigates data insufficiency problems and decreases the severity of artifacts. However, the use of smaller cone angles also results in reduced image magnification, which in turn results in decreased spatial resolution. The use of multiple pinholes allows a greater number of photons to pass through the multiple pinhole collimator thereby improving sensitivity. However, the number of pinholes that may be used is limited since the use of too many pinholes may result in the overlapping of projected images on the detector thereby reducing the quality of the tomographic information content in the projection data.
Thus what is needed is a collimator and method of configuring the collimator for use with a gamma ray imaging device to overcome one or more of the challenges and/or obstacles described above.